Assembly and function of claudins: Structure-function relationships based on homology models and crystal structures.

Area of Science:

• Cell biology
• Structural biology
• Biochemistry

Background:

• Claudins are tetra-span transmembrane proteins crucial for tight junction (TJ) formation and function.
• They regulate paracellular permeability and tightness between epithelial and endothelial cells through homo- and heterophilic interactions.
• Twenty-seven claudin subtypes exhibit tissue-specific regulation of TJ properties.

Purpose of the Study:

• To review the functional impact of specific claudin residues.
• To correlate these functional impacts with structural features and architectural characteristics.
• To elucidate the molecular mechanisms of TJ assembly and paracellular permeability regulation.

Main Methods:

• Analysis of structural data from homology models, cryo-electron microscopy, and crystal structures.
• Dissection of claudin contributions by transmembrane region, extracellular loop 1, and extracellular loop 2.
• Survey of claudin impact on oligomerization and TJ strand/pore formation.

Main Results:

• Specific claudin residues significantly influence TJ function.
• Structural features of transmembrane and extracellular regions dictate claudin contributions.
• Claudin interactions are critical for oligomerization and the formation of TJ strands and pores.

Conclusions:

• Detailed structure-function relationships of claudins are key to understanding TJ assembly.
• Elucidating these relationships provides insights into the regulation of paracellular permeability.
• Further research is needed to fully understand the molecular mechanisms involved.